We plan to study the regulation of lysosomal hydrolase levels in rat pulmonary tissue. Previous work from our laboratory has demonstrated that lysosomal glycosidases are rapidly cleared from the circulation by nonparenchymal cells in the liver. We have now extended this by demonstrating that alveolar macrophages have a specific uptake system for lysosomal glycosidases and other glycoproteins that can be studied in vitro. Uptake requires the non-reducing sugars of a potential ligand to be mannose or glucose and has recognition characteristics similar to the in vivo clearance. We propose to characterize the alveolar macrophage uptake kinetically and to study the cellular processes involved. We also plan to purify a number of lysosomal hydrolases from rat pulmonary tissue an determine if they are taken up by alveolar macrophages. An important aspect of this study will be to determine if different pathways for uptake exist for the classes of lysosomal enzymes (e.g., glycosidases versus proteases). We hope to be able to delineate the role of specific recognition sites and cell surface receptors in the endocytosis, transport and distribution of lysosomal hydrolases in normal physiologic processes.